Dentifrice compositions

ABSTRACT

It is disclosed that a dentifrice which includes a surfactant and an anti-plaque agent comprising a substantially water-insoluble non-cationic antimicrobial agent or a zinc salt or a mixture thereof has enhanced activity when the dentifrice comprises at least 0.2% by weight of a lamellar liquid crystal surfactant phase having a lamellar spacing of less than 6.0 nm.

This invention relates to dentifrice compositions, more particularly todental creams or gels, for inhibiting the formation of dental plaque.

It is now established that there is a relationship between dental plaqueand gingival inflammation. At present, mechanical cleaning bytoothbrushing is the most widely used method of removing plaque.However, the relatively short period of brushing commonly practised isinsufficient to achieve adequate removal of plaque especially from areasleast accessible to brushing.

The dental literature over the last 25 years is replete withpublications concerned with the use of organic antimicrobial agents tocombat dental plaque. Most work has concentrated on the use of cationicagents because these are substantive to oral tissues and are thereforeretained in the mouth. It is believed that their activity is due totheir being adsorbed onto oral surfaces and gradually released over aperiod of time (Journal of Clinical Periodontology 1980: 7 431-442).Unless an active antimicrobial agent is adsorbed onto oral surfaces theoral bacteria in the mouth rapidly recover and no significant reductionin plaque growth would be expected (British Dental Journal March 1984,175-178). However, the successful formulation of a cationicantimicrobial agent into a commercially acceptable toothpaste has notyet been achieved and this is at least in part due to theincompatibility of cationic antimicrobial agents with common toothpasteingredients. In addition, cationics, especially chlorhexidine which hasbeen extensively investigated, have the further disadvantage of causingtooth staining as well as having a long-lasting bitter taste. Manycationics also cause irritation of the oral tissues. Attempts toovercome the tooth staining problem are the subject of many patents. Webelieve that there is to date no commercial toothpaste containing anorganic cationic antimicrobial agent which is recognised as having asignificant anti-plaque benefit.

Although there are references in the literature to attempts to useantimicrobial agents other than cationic compounds for providing animprovement in oral health it is generally considered that the oralsubstantivity of these agents is not sufficient to provide a significantantiplaque benefit and they are in any case considered unattractivebecause of their generally poor water-solubility. Hitherto it has beenthe general belief that it is necessary for the active agent of adentifrice to be in solution in the aqueous phase of the toothpaste.

We have now discovered that it is possible to obtain substantialreductions in plaque growth by means of a substantially water-insolublenon-cationic antimicrobial agent, or mixture of antimicrobial agents,provided the dentifrice composition containing it has certaincharacteristics of which details are given below. Such unexpectedanti-plaque activity we believe is due to the fact that the specialdentifrice composition of the invention is able to deliver theantimicrobial agent to tooth surface where it is retained for a timesufficient to materially affect the rate of plaque regrowth, rate ofplaque metabolism and equilibrium plaque level.

Our research has also shown that our special dentifrice composition isalso able to lead to an enhanced retention in the mouth of zinc salts,generally known to have an anti-plaque effect, resulting in animprovement in effectiveness in inhibiting plaque growth. Various zincsalts, for example zinc citrate, are referred to in U.S. Pat. No.4,022,880. The use of zinc carboxymethyloxysuccinate is referred to inU.S. Pat. No. 4,144,323.

According to the present invention there is provided a dentifricecomposition effective to inhibit the growth of dental plaque comprisinga surfactant and an anti-plaque agent consisting of a substantiallywater-insoluble non-cationic antimicrobial agent or a zinc salt having awater solubility greater than 2×10⁻⁴ g, preferably greater than 1×10⁻²g, per 100g of water at 25° C. and at pH7, or a mixture thereof,characterised in that there is present in the dentifrice composition alyotropic lamellar liquid crystal phase comprising alternate layers ofsurfactant molecules and water molecules (and hereinafter referred to asa lamellar liquid crystal surfactant phase) having a lamellar spacing ofless than 6.0 nm, the lamellar liquid crystal surfactant phase beingpresent in an amount of at least 0.2%, preferably at least 0.3%, andmore preferably at least 0.5%, by weight of the dentifrice composition.

The determination of whether a dentifrice composition comprises alamellar liquid crystal surfactant phase can be determined byexamination of the product obtained by subjecting the dentifrice to acentrifuge separation procedure, which will now be described.

The dentifrice is centrifuged with sufficient centrifugal force toseparate the main phases present which usually are abrasive, aqueous,detergent and flavour phases. A preliminary centrifugation is convenientto separate the majority of the abrasive, followed by anultracentrifugation to separate the phases of the liquid portion. Thespeed and duration of the centrifugation required is dependent upon theresistance of the formulation towards separation. The separation of adentifrice containing sodium carboxymethylcellulose as binder isfacilitated by degrading the binder enzymatically prior tocentrifugation. The dentifrice is incubated with cellulase-containingpowder (0.1% w/w, prepared from Aspergillus niger, activity 1.3units/mg) for 18 hours at room temperature to degrade the sodiumcarboxymethylcellulose binder.

The resultant slurry or the dentifrice itself, if no preliminarydegradation of the binder is carried out, is centrifuged at 10,000 xgfor 1 hour and the sedimented abrasive removed. The liquid portion isthen ultracentrifuged at 200,000xg for 2 hours or until there is nosubstantial change in the volumes of the separated layers. Theseconditions of centrifugation have generally been found to besatisfactory for separating the phases of a dentifrice although longerperiods of centrifugation and ultracentrifugation may sometimes benecessary.

The product obtained by this centrifuge procedure is referred to hereinas the centrifuge separation product. The centrifuge separation productwill consist of a number of layers. The lower layer of solids and thehumectant-containing layer above it will together constitute the majorpart of the centrifuge separation product. The remainder of thecentrifuge separation product may include a layer consistingpredominantly of surfactant in the form of liquid crystals. If present,this layer will generally constitute the upper layer or one of the upperlayers. Its actual position will depend on the relative densities of thelayers. This layer constituting the liquid crystal surfactant phase ofthe dentifrice can be removed from the centrifuge separation product andits weight as a percentage of the dentifrice determined. The lamellarliquid crystal surfactant phase is basically made up of layers ofsurfactant molecules separated by water layers but may comprise othercomponents depending upon the overall composition of the dentifrice. Thedistribution of such other components between the surfactant and waterlayers will depend upon their respective aqueous solubilities andhydrophobicities.

Liquid crystals are well known and a recent book describing them isentitled "Aggregation Processes in Solution" edited by E Wyn-Jones and JGormally published by Elsevier Scientific Publishing Company,Amsterdam-Oxford-New York 1983, and particular reference is made toChapter 7 entitled "Lyotropic Liquid Crystals".

If the centrifuge separation product comprises a lamellar liquid crystalsurfactant phase then the layer spacing can be determined by an X-rayscattering technique.

The layer spacing, d_(o), is defined as the distance between repeatunits in the cross-section of a layered liquid crystal structure, i.e.,the combined thickness of the detergent sheet and of the water layersandwiched between the detergent sheets. It can be measured by SmallAngle X-ray Scattering (SAXS), a technique used to determine longperiodicities in the range 1 nm-1,000 nm in crystalline or liquidcrystal materials. The `Kratky` SAXS camera used in such work produces,through a sophisticated collimation system, a fine beam of X-rays (Cu,K.sub.α radiation) which impinge on the sample contained in a 1 mm glasscapillary or sandwiched between 6μ thick Mylar film.

The scattered radiation is detected by a proportional counter whichdetermines the variation in scattered intensity with respect to angle.The angle corresponding to the peak maximum is measured from the chartrecorder trace and the corresponding `d-spacing` is calculated fromBragg's equation

    2d sin θ=n 80

with n=1, λ=0.1542 nm for Cu K.sub.α radiation.

Applications of this technique for the measurement of the lamellarspacing of lamellar liquid crystal phases are described in Journal ofColloid and Interface Science, Vol. 41, No. 1, April 1974, pages 59 to64 and Vol. 86, No. 2, April 1982, pages 501 to 514.

The lamellar spacing of the liquid crystal surfactant phase of adentifrice according to the present invention is preferably less than5.0 nm, more preferably less than 4.4 nm.

Dentifrices usually comprise an anionic surfactant and most commonlyused is sodium lauryl sulphate derived from coconut fatty acidscomprising mainly sodium dodecyl sulphate, although pure sodium dodecylsulphate can be used. Sodium dodecylbenzene sulphonate is another knowndentifrice surfactant although it is not usually employed as the solesurfactant of a dentifrice. It may be used in combination with sodiumlauryl sulphate. Suitable combinations of sodium lauryl sulphate andsodium dodecyl benzene sulphonate are in the proportions 4:1 to 1:4 byweight. The use of a combination of these surfactants in a dentifricecomprising a zinc-containing anti-plaque agent is described in GB-A No.1 373 003. Sodium lauroyl sarcosinate is another well-known dentifricesurfactant that may also be employed in dentifrices of this invention.

The surfactant in a dentifrice can be present in three main forms, as asolution, a liquid crystal phase or crystalline solid. The form or formsin which the surfactant is present depends particularly on the otheringredients of the dentifrice. Thus in the presence of glycerol, whichis very commonly used as the sole or major humectant liquid, thesurfactant will generally be present as a solution since glycerol is asolvent for common dentifrice surfactants. The same applies to propyleneglycol, also a well-known dentifrice humectant. We have also found thatwhen sorbitol is employed as the humectant then in the absence of aflavour oil the surfactant is present as a solid crystalline phase dueto its poor solubility in sorbitol solution. However, in the presence offlavour oil the solid crystalline surfactant phase is converted into alamellar liquid crystal phase. Thus dentifrice formulations that promotethe formation of a liquid crystal surfactant phase are those based onthe use of sorbitol as the humectant and which also contain a flavouroil. However, the use in combination with sorbitol of such amounts ofglycerol that do not prevent the formation of a liquid crystalsurfactant phase is permissible. Other ways of producing a lamellarliquid crystal surfactant phase are, of course, within the scope of thepresent invention.

The layer spacing of a liquid crystal surfactant phase in a dentifriceis influenced by the electrolyte concentration of the aqueous phase.Thus the obtaining of a layer spacing of less than 6.0 nm in accordancewith this invention can be effected by control of the electrolyteconcentration of the aqueous phase. In order to achieve such a lowlamellar spacing the electrolyte concentration needs to be relativelyhigh. However, means other than control of electrolyte concentration maybe employed to control lamellar spacing.

An appropriate concentration of the electrolyte can be produced by theaddition of a suitable water-soluble electrolyte. Only simpleexperimentation is required to determine the amount of electrolyterequired to give a low d_(o) value. In general, any non-toxic salt ormixture of salts that is compatible with the therapeutic ingredient oringredients, as well as with the other dentifrice components, and isorganoleptically acceptable can be used. The salt that is referred tohere is in addition to any fluorine-containing salt which may beincluded to give an anti-caries benefit. Such salt is of course, inaddition to the surfactant (which is also an electrolyte) and any zincsalt which may also be present. The additional salt is also to bedistinguished from a binder or thickener for the aqueous humectantliquid phase, said binder or thickener being a commonly employeddentifrice ingredient and which may be constituted by a salt, e.g.,sodium carboxymethylcellulose. The surfactant, binder andfluorine-containing salts when employed at conventional levels do notproduce, even in combination, a sufficient concentration of electrolyteto reduce the layer spacing of a surfactant liquid crystal phase tobelow 6.0 nm.

The cation of the added salt is preferably sodium, potassium, aluminium,magnesium or zinc. Suitable anions are acetate, chloride, citrate,gluconate, lactate, sulphate, phosphate, tartrate, glyconate andascorbate. Some salts are more effective than others in reducing thed_(o) value at the same molar cation addition. Preferred salts are thoseof sodium and aluminium.

We have found that the amount of sodium chloride added is suitably inthe range from about 0.1 to about 3%, preferably about 0.1 to about 1%,by weight of the dentifrice composition. Other salts may be added insuch amounts that the total cation molar concentration corresponds tothose for sodium chloride previously given.

It is not advisable to include any more salt than is necessary toproduce the desired low lamellar spacing. Excessive amounts may not onlyimpair the organoleptic qualities of the dentifrice but in fact willresult in the destruction of the liquid crystal phase. We have foundthat a liquid crystal surfactant phase may be destroyed on the additionof 5% sodium chloride. Consequently, it is recommended that the amountof any added electrolyte should not exceed the cation molar equivalentof about 3% by weight of the dentifrice of sodium chloride. In practice,an optimum reduction in layer spacing can be achieved at levels ofaddition of sodium chloride substantially less than 3% by weight.

A zinc salt, if present, will contribute to the total electrolyteconcentration of the aqueous phase.

A part of the electrolyte present in the aqueous phase may be composedof ions originating from a solid abrasive agent, for example aluminiumions from an alumina abrasive, and the proportion of such ions in theaqueous phase can be dependent upon the type of mixer employed, moreespecially upon the energy employed in mixing the solid componentsduring the manufacture of the dentifrice.

The dentifrices of this invention generally have a weight of liquidcrystal surfactant phase of at least 1% and they typically have acontent thereof of from 1.5 to 12% by weight.

The antiplaque agent of the dentifrice of the invention is asubstantially water-insoluble non-cationic antimicrobial agent or a zincsalt as defined above or a mixture thereof. By a substantiallywater-insoluble antimicrobial agent is meant herein one having asolubility in water at 25° C. of less than 1%, preferably less than 0.5%and more preferably less than 0.1%, save that if the antimicrobial agentcontains ionisable groups the solubility is determined at a pH at whichsuch groups are not ionised. The antimicrobial agents employed indentifrice compositions of this invention can be regarded as essentiallynon-ionic in character. However, many suitable antimicrobial compoundscontain one or more phenolic hydroxy groups which may be ionisable atcertain pHs and therefore it is considered more exact to describe thegeneral class of antimicrobial agents useful in the dentifricecomposition of this invention as being non-cationic in nature.

Examples of classes of non-cationic antimicrobial agents which may beemployed in the dentifrice composition of the invention are the phenolicand bisphenolic compounds, halogenated diphenyl ethers, benzoate estersand carbanilides.

Illustrative of the phenolic antimicrobial compounds, which include thehalogenated salicylanilides, are

2-phenylphenol

4-chlorophenol

4-chloro-2-methylphenol

4-chloro-3-methylphenol

4-chloro-3,5-dimethylphenol

2,4-dichloro-3,5-dimethylphenol

3,4,5,6-tetrabromo-2-methylphenol

5-methyl-2-pentylphenol

4-isopropyl-3-methylphenol

5-chloro-2-hydroxydiphenylmethane

4',5-dibromosalicylanilide

3,4',5-trichlorosalicylanilide

3,4',5-tribromosalicylanilide

2,3,3',5-tetrachlorosalicylanilide

3,3',4,5'-tetrachlorosalicylanilide

3,5-dibromo-3'-trifluoromethylsalicylanilide

5-n-octanoyl-3'-trifluoromethylsalicylanilide

Among the bisphenolic compounds may be mentioned

2,2'-methylenebis(3,4,6-trichlorophenol)

2,2'-methylenebis(4-chlorophenol)

2,2'-methylenebis(4-chloro-6-bromophenol)

bis(2-hydroxy-3,5-dichlorophenyl) sulphide

bis(2-hydroxy-5-chlorophenyl) sulphide.

These antibacterial agents may be employed in the form of their zincderivatives many of which are disclosed in U.S. Pat. No. 4,022,880.

Exemplifying the class of the halogenated hydroxydiphenyl ethers are thecompounds 2',4,4'-trichloro-2-hydroxy-diphenyl ether and2,2'-dihydroxy-5,5'-dibromo-diphenyl ether.

Another well-known class of non-cationic antimicrobial agents are theesters of p-hydroxybenzoic acid, especially the methyl, ethyl, propyl,isopropyl, butyl, isobutyl, hexyl, heptyl and benzyl esters.

Halogenated carbanilides can also be used, which class is typified by

3,4,4'-trichlorocarbanilide

3-trifluoromethyl-4,4'-dichlorocarbanilide

3,3',4-trichlorocarbanilide

Other known substantially water-insoluble non-cationic antimicrobialagents can also be used, for example 2,4-dichlorobenzyl alcohol,3,4-dichlorobenzyl alcohol and 3-(4-chlorophenoxy)-propan-1,2-diol.

The preferred antimicrobial agents are halogenated bisphenoliccompounds, and the halogenated hydroxydiphenyl ethers. Especiallypreferred are 2',4,4'-trichloro-2-hydroxy-diphenyl ether (hereafterreferred to as Triclosan) and 2,2'-methylenebis(4-chloro-6-bromophenol).

The above-mentioned antimicrobial agents which are suitable for use indentifrices are not antibiotics. Antibiotics are not generally used soas to avoid the risk of resistant strains of bacteria developing.

The antimicrobial agent will usually be used in an amount of 0.01 to 5%,preferably 0.05 to 1% by weight of the dentifrice. A mixture ofantimicrobial agents may of course be used.

The anti-plaque agent of the dentifrice composition of the inventionalternatively may be a zinc salt having a water solubility greater than2×10⁻⁴ g, preferably greater than 1×10⁻² g, per 100 g of water at 25° C.and at pH7. Many suitable zinc salts are described in U.S. Pat. No.4,022,880. Preferred zinc salts are those of mono-, di- andtricarboxylic acids, alpha-hydroxy carboxylic acids and amino acidsExamples of preferred salts are zinc citrate, zinc tartrate, zincmalate, zinc lactate, zinc glycinate, zinc glycolate, zinc succinate,zinc carboxymethyloxysuccinate, zinc gluconate, zinc salicylate, zinchistamine and zinc histidine. Ammonium and alkali metal zinc citrates asdescribed in U.S. Pat. No. 4,325,939 may also be used. More than onezinc salt can be of course be employed.

The zinc salt, or mixture of zinc salts, is desirably used in an amountsuch as to provide in the dentifrice from about 0.05 to about 1.5% byweight of zinc.

The preferred zinc salt is zinc citrate. This is readily available asthe trihydrate. This is preferably incorporated in an amount of about0.2 to about 5% by weight, and for best organoleptic acceptability mostpreferably 0.2 to 2% by weight.

Best results are obtained by using an antimicrobial agent in combinationwith a zinc salt, such as zinc citrate. Most preferred antiplaquesystems are based on the combination of Triclosan and zinc citrate andthe combination of 2,2'-methylenebis(4-chloro-6-bromophenol) and zinccitrate. Combinations of an antimicrobial agent and zinc citrate givethe best degree of plaque growth inhibition, the most preferredcombination being that of Triclosan and zinc citrate. With the lattercombinaticn a plaque inhibition approaching that obtainable withchlorhexidine has been obtained without the severe drawbacks associatedwith the use of that cationic material.

A particularly preferred dentifrice composition according to theinvention comprises 0.05 to 0.3% Triclosan, 0.3% to 1.5% zinc citrate,0.2 to 1% sodium chloride and 1 to 3% sodium lauryl sulphate.

The dentifrice composition of the invention preferably also comprises aparticulate abrasive agent compatible with the active ingredients of thetoothpaste. Especially preferred are hydrated alumina and silicaabrasives, both of which are widely employed in commercial products. Theparticle size of the abrasive agent will usually be in the range 2 to 20microns as is customary. Suitable grades of alpha-alumina trihydrate aresold under the name BACO by BA Chemicals of Great Britain and under thename MARTINAL by Martinswerke GmbH of Germany. Preferred silicaabrasives are the well-known silica xerogels, for example GASIL 200(sold by Crosfield Chemicals, Great Britain) and SYLOID 63 (sold byGrace Corporation USA), and precipitated silicas, for example ZEO 49(sold by the Huber Corporation USA). The amount of abrasive agentemployed will usually be between 5 and 60% by weight of the dentifricecomposition.

Suitable binders or thickeners for use in dentifrice compositions areknown to those skilled in the art. Commonly used are sodiumcarboxymethylcellulose and xanthan gum. For flavouring dentifricespeppermint and spearmint oils are commonly used, although a wide varietyof other oils also find application. Flavour oils are usually present inan amount of from 0.1 to 5% by weight. Apart from the above generallystandard ingredients, a number of optional ingredients may also beincluded, especially fluoride, such as sodium monofluorophosphate orsodium fluoride, opacifying agent, e.g. titanium dioxide, preservative,sweetening agent and a pH-adjusting agent.

The water content of the dentifrices in accordance with this inventionwill generally be between about 25 and 60% by weight of the dentifriceexcluding insoluble solids.

The dentifrices of the invention can be made by conventional methods.Since the obtaining of a low d_(o) spacing of a liquid crystalsurfactant phase is controlled by the concentration of the electrolytein the aqueous phase of the final toothpaste composition, water lossduring manufacture affects the electrolyte concentration. It istherefore desirable to avoid the use or production of excessivetemperatures during manufacture and preferably the temperature ofprocessing is within the range 15° to 35° C., more preferably 22° to 32°C.

The present invention in one aspect relates to a process for making adentifrice composition which includes added sodium chloride or otherwater-soluble salt, which process comprises mixing the water-solublesalt with the other ingredients so as to result in an aqueous phasehaving an electrolyte concentration sufficient to result in theformation of a liquid crystal surfactant phase having a lamellar spacingof less than 6.0 nm, the dentifrice ingredients preferably being mixedat a temperature within the range 15° to 35° C., more preferably 22° to32° C.

The following Examples illustrate the invention. Percentages are byweight.

EXAMPLE 1

A number of toothpastes were made from the following ingredients.

    ______________________________________                                        Ingredient           %                                                        ______________________________________                                        Alumina trihydrate   50.000                                                   Sorbitol syrup (70% solution)                                                                      27.000                                                   Sodium lauryl sulphate                                                                             1.875                                                    Sodium dodecylbenzenesulphonate                                                                    0.625                                                    Sodium carboxymethylcellulose                                                                      0.800                                                    Zinc citrate trihydrate                                                                            1.000                                                    Triclosan            0.500                                                    Sodium monofluorophosphate                                                                         0.850                                                    Flavour oil          1.200                                                    Sodium saccharinate  0.180                                                    Formalin BP          0.040                                                    Water                to 100.000                                               ______________________________________                                    

The toothpastes were made using a variety of toothpaste mixers somemixers having a greater energy of mixing than others. In some casesthere was more water loss than others. This together with differingamounts of cations from the abrasive which passed into solution resultedin the toothpastes having differing electrolyte concentrations. In eachcase the surfactant was present in the toothpaste in the form of aliquid crystal phase but the lamellar spacings were different for thedifferent toothpastes as a consequence of the differing electrolyteconcentration of the aqueous phase of the final products. In themanufacture of the toothpastes of this Example, and of those of allsubsequent Examples, the ingredients are mixed at a temperature withinthe range 22° to 32° C. The values for the lamellar spacing, d_(o), aregiven in Table I below. These values, and all other d_(o) values givenherein, are those determined within a month of manufacture of therespective toothpaste.

Also given in Table I are PG values for the respective products. PGstands for Plaque Growth and the smaller the PG value the greater theefficacy of the toothpaste to inhibit the growth of plaque on the teeth.The PG value is determined from data obtained when following a standardprocedure for the measurement of plaque growth. The methodology ofmeasuring plaque growth is that according to Harrap as described inJ.Clin.Periodontol., 1974, 1, 166-174 which gives a procedure forassessing the amount of plaque on the teeth adjacent to the gingivalmargin. The procedure is as follows:

During the late afternoon each subject brushes his teeth with a simple,non-active paste (having a composition as given hereinafter) for anunspecified period of time to remove as much plaque as possible. This isimmediately followed by brushing for one minute with 1.5 g of theallocated test paste. Residual paste is removed by rinsing the mouthwith water and any remaining plaque disclosed by painting the teeth withan aqueous solution of Erythrosin (0.5% w/w) using a soft camel hairbrush. Excess dye is removed by rinsing with water and the amount ofplaque assessed and recorded for each of 16 teeth (numbers 3 to 6 foreach quadrant). The recorded plaque is designated P₀.

No further oral hygiene is permitted for 18 hours after which time eachsubject rinses his mouth with water to remove food debris and viscoussaliva. Plaque assessment is then carried out as before and recorded(P₁₈). The values of P₁₈ -P₀ for each tooth are averaged to give a P₁₈-P₀ value per mouth. The mean of the values obtained for the subjects inthe test is the PG value. Panels of at least 12 subjects are used. ThePlaque Growth value for a toothpaste without active ingredients isusually in the range 22 to 26.

The composition of the simple, non-active toothpaste referred to abovewas the following:

    ______________________________________                                        Ingredient       %                                                            ______________________________________                                        Alumina trihydrate                                                                             50.00                                                        Glycerin         27.00                                                        Hydroxyethylcellulose                                                                           0.95                                                        Titanium dioxide  0.50                                                        Water            to 100.00                                                    ______________________________________                                    

The lamellar spacings and PG values for the toothpastes that wereformulated are presented in Table I in the order of the magnitude of thelamellar spacings.

                  TABLE I                                                         ______________________________________                                        Lamellar spacing of Liquid                                                                         PG                                                       Crystal Sufactant Phase (nm)                                                                       Value                                                    ______________________________________                                        6.6                  19.9                                                     6.3                  18.5                                                     6.1                  16.8                                                     5.6                  16.1                                                     5.0                  15.6                                                     4.8                  14.5                                                     4.6                  13.4                                                     4.3                  12.4                                                     4.0                  12.0                                                     ______________________________________                                    

This shows that as the d_(o) value decreases the effectiveness of thetoothpaste in inhibiting plaque growth increases.

The amounts of the liquid crystal surfactant phase for the abovetoothpastes all exceeded 1.5% by weight of the respective toothpaste.

EXAMPLE 2

This example shows the beneficial decrease in the PG value that can beobtained by the addition of a relatively minor amount of electrolyte.

Various toothpastes containing sodium chloride were made employing theingredients listed in Table II.

                  TABLE II                                                        ______________________________________                                                     Toothpaste                                                       Ingredient     A           B        C                                         ______________________________________                                        Alumina trihydrate                                                                           50.000      50.000   50.000                                    Sorbitol syrup (70%)                                                                         27.000      27.000   27.000                                    Sodium lauryl sulphate                                                                       1.875       1.875    1.875                                     Sodium dodecylbenzene                                                                        0.625       0.625    0.625                                     sulphonate                                                                    Sodium         0.850       0.850    0.800                                     carboxymethylcellulose                                                        Zinc citrate trihydrate                                                                      0.500       0.500    0.500                                     Triclosan      0.200       0.200    0.200                                     Sodium chloride                                                                              0.500       0.500    0.500                                     Titanium dioxide                                                                             0.500       --       --                                        Sodium         0.850       0.850    0.850                                     monofluorophosphate                                                           Sodium saccharin                                                                             0.180       0.180    0.180                                     Formalin BP    --          0.040    0.040                                     Flavour oil    1.200       1.200    1.200                                     Water          to 100.000  100.000  100.000                                   ______________________________________                                    

Corresponding toothpaste A', B' and C' were made from which the sodiumchloride was omitted.

The toothpastes of each pair of tootpastes A A', B,B' and CC' were madein an identical manner using the same mixer. The respective pairs weremanufactured using commercial mixer types, respectively Thompson,Pressindustria and Fryman mixers.

Table III shows that in each case the inclusion of the sodium chlorideresulted in an improvement in effectiveness in Inhibiting plaque growth.

                  TABLE III                                                       ______________________________________                                        Toothpaste    Difference in                                                                            Difference in                                        Pair          d.sub.o (nm).sup.1                                                                       PG values.sup.2                                      ______________________________________                                        A,A'          3.5        6.3                                                  B,B'          3.1        5.6                                                  C,C'          3.3        4.3                                                  ______________________________________                                         .sup.1 the saltcontaining toothpastes comprised surfactant liquid crystal     phase with smaller d.sub.o values than the respective toothpastes not         containing salt                                                               .sup.2 the saltcontaining toothpastes gave lower PG values than the           respective toothpastes not containing salt                               

The amount of the liquid crystal surfactant phase in each of the sixtoothpastes exceeded 2% by weight.

EXAMPLE 3

A toothpaste was made from the same ingredients as for toothpaste A ofExample 2 save that in place of Triclosan was employed the followingantimicrobial agent:

    ______________________________________                                        Toothpaste       Antimicrobial agent                                          ______________________________________                                        D                2,2'-methylenebis(3,4,6-                                                      trichlorophenol)                                             ______________________________________                                    

Table IV gives the d_(o) value, percentage weight of the liquid crystalsurfactant phase and PG value for the toothpaste.

                  TABLE IV                                                        ______________________________________                                                  d.sub.o     % wt liquid                                                                              PG                                           Toothpaste                                                                              (nm)        crystal phase                                                                            value                                        ______________________________________                                        D         4.1         3.7        11.5                                         ______________________________________                                    

EXAMPLE 4

This example illustrates the use of further antimicrobial agents.

Toothpastes were formulated as for toothpaste C of Example 2, ortoothpaste A as indicated, save that the antimicrobial agents listed inTable V were used in place of Triclosan. The lamellar spacings, d_(o),of the liquid crystal surfactant phase of each toothpaste is also givenin Table V along with the percentage weight of the liquid crystalsurfactant phase.

                  TABLE V                                                         ______________________________________                                                                    % wt liquid                                       Antimicrobial Agent d.sub.o (nm)                                                                          crystal phase                                     ______________________________________                                        3,4',5-tribromosalicylanilide                                                                     4.1     3.0                                               3,4,4'-trichlorocarbanilide                                                                       4.1     2.4                                               bis(2-hydroxy-5-chlorophenyl)                                                                     4.1     0.8                                               sulphide                                                                      5-methyl-2-pentylphenol                                                                           4.0     1.7                                               2,4-dichlorobenzyl alcohol                                                                        4.2     1.6                                               4-chloro-3,5-dimethylphenol                                                                       4.2     2.0                                               5-chloro-2-hydroxydiphenyl                                                                        3.9     0.9                                               methane                                                                       5-n-octanoyl-3'-trifluoromethyl                                                                   4.0     2.9                                               salicylanilide                                                                n-butyl-p-hydroxybenzoate*                                                                        3.6     3.8                                               2,2'-methylenebis(4-chloro-                                                                       4.0     4.0                                               6-bromophenol)*                                                               ______________________________________                                         *formulated as for toothpaste A of Example 2                             

EXAMPLE 5

This example shows that a wide variety of electrolytes can be used tolower the d_(o) spacing of a liquid crystal surfactant phase of atoothpaste.

A series of toothpastes were made having the ingredients of toothpaste Cof Example 2 save that the sodium chloride was replaced by another saltas indicated in Table VI below. This table also gives the d_(o) spacingsfor the liqid crystal surfactant phase of each toothpaste, and thepercentage weight of the liquid crystal surfactant phase.

                  TABLE VI                                                        ______________________________________                                                                          % wt liquid                                 Salt           % w/w      d.sub.o (nm)                                                                          crystal phase                               ______________________________________                                        Potassium chloride                                                                           0.64       3.5     3.6                                         Magnesium sulphate 7H.sub.2 O                                                                2.11       4.5     2.5                                         Potassium lactate                                                                            1.10       3.6     1.4                                         Potassium tartrate 0.5H.sub.2 O                                                              1.01       3.7     2.1                                         Sodium acetate 0.70       3.5     3.0                                         Sodium ascorbate                                                                             1.69       3.8     3.2                                         Sodium lactate 0.96       3.8     3.0                                         Sodium sulphate                                                                              0.61       4.2     2.9                                         Trisodium citrate 2H.sub.2 O                                                                 0.84       3.6     3.0                                         Potassium gluconate                                                                          2.00       3.3     1.7                                         Disodium hydrogen                                                                            1.53       3.9     3.4                                         orthophosphate 12H.sub.2 O                                                    Potassium acetate                                                                            0.84       3.6     1.2                                         Sodium glycinate 1H.sub.2 O                                                                  0.98       3.9     2.7                                         Sodium gluconate                                                                             1.87       3.9     2.2                                         Sodium tartrate 2H.sub.2 O                                                                   0.99       4.0     2.2                                         ______________________________________                                    

In each case the amount of salt incorporated was equivalent to the samemolar cation concentration as 0.5% sodium chloride.

The d_(o) values for toothpastes C and C' were 3.9 nm and 7.2 nm,respectively.

EXAMPLE 6

This example shows the effect on the lamellar spacing of a liquidcrystal surfactant phase of a dentifrice of including increasing amountsof sodium chloride in the dentifrice formulation up to 1% by weight ofthe dentifrice. The dentifrice comprised the following ingredients.

    ______________________________________                                        Ingredients          %                                                        ______________________________________                                        Alumina trihydrate   50.000                                                   Sorbitol Syrup (70% solution)                                                                      27.000                                                   Sodium lauryl sulphate                                                                             1.875                                                    Sodium docecylbenzene sulphonate                                                                   0.625                                                    Sodium carboxymethylcellulose                                                                      0.800                                                    Zinc citrate trihydrate                                                                            0.500                                                    Triclosan            0.200                                                    Sodium monofluorophosphate                                                                         0.850                                                    Sodium saccharinate  0.180                                                    Formalin BP          0.040                                                    Flavour oil          1.200                                                    Sodium chloride      see Table                                                Water                To 100.000                                               ______________________________________                                    

The d_(o) values are given in Table VIII together with percentageweights of the liquid crystal phase.

                  TABLE VII                                                       ______________________________________                                                                 % wt liquid                                          % sodium chloride                                                                              d.sub.o (nm)                                                                          crystal phase                                        ______________________________________                                        0.000            7.5     2.1                                                  0.100            7.4     2.0                                                  0.200            6.4     1.4                                                  0.300            4.8     1.1                                                  0.400            4.1     1.0                                                  0.500            4.1     1.1                                                  1.000            3.8     1.7                                                  ______________________________________                                    

All the toothphases were made in the same way, the amount of the sodiumchloride being the only variable.

EXAMPLES 7 to 11

The following are further examples of dentrifrice formulations of theinvention that have been made.

    ______________________________________                                                   %                                                                  Ingredient                                                                            Example: 7       8     9     10    11                                 ______________________________________                                        Alumina trihydrate                                                                         50.000  50.000  50.000                                                                              50.000                                                                              --                                   Silica xerogel                                                                             --      --      --    --    10.000                               (Gasil 200)                                                                   Precipitated silica                                                                        --      --      ----  8.000                                      (Sipernat 22S)                                                                Sorbitol syrup (70%)                                                                       27.000  27.000  27.000                                                                              27.000                                                                              45.500                               Sodium lauryl                                                                              1.875   2.500   1.875 1.875 2.400                                sulphate                                                                      Sodium dodecyl-                                                                            0.625   0.500   0.625 0.625 0.800                                benzene sulphonate                                                            Sodium carboxy-                                                                            0.850   --      0.800 0.800 0.800                                methylcellulose                                                               Xanthan gum  --      1.000   --    --    --                                   Zinc citrate trihydrate                                                                    1.000   0.500   0.500 --    0.500                                Sodium zinc citrate                                                                        --      --      --    2.785 --                                   preparation.sup.1                                                             Triclosan    0.200   0.120   0.200 0.500 0.200                                Sodium chloride                                                                            0.500   --      --    --    1.000                                Titanium dioxide                                                                           0.500   1.000   --    --    --                                   Sodium monofluoro-                                                                         0.850   1.200   0.850 0.850 1.120                                phosphate                                                                     Sodium saccharin                                                                           0.180   0.180   --    0.180 0.300                                Sodium cyclamate                                                                           --      --      2.000 --    --                                   Formalin BP  0.040   0.040   0.040 0.040 --                                   Flavour oil  1.200   1.200   1.200 1.200 1.200                                Colour       0.008   0.007   --    --    --                                   Water   to   100.000 100.000 100.000                                                                             100.000                                                                             100.000                              ______________________________________                                         .sup.1 an aqueous premix of 1.41% trisodium citrate dihydrate and 1.375%      zinc sulphate heptahydrate                                               

    Example:                                                                                    7       8       9    10    11                                   ______________________________________                                        d.sub.o spacing (nm)                                                                        4.0     3.9     3.8  3.7   3.5                                  Plaque growth value                                                                         12.7    13.1    --   10.7  --                                   % wt liquid crystal phase                                                 

EXAMPLES 12 to 14

The following are yet further examples of dentifrice formulations of theinvention.

    ______________________________________                                                          Parts by weight                                             Ingredient     Example: 12      13    14                                      ______________________________________                                        Alumina trihydrate  50.00   50.00   50.00                                     Sorbitol syrup (70%)                                                                              27.00   27.00   27.00                                     Sodium lauryl sulphate                                                                            --      1.50    0.75                                      Sodium dodecylbenzene                                                                             2.00    --      0.75                                      sulphonate                                                                    Zinc citrate trihydrate                                                                           1.00    1.00    1.00                                      Triclosan           0.50    0.50    0.50                                      Sodium chloride     1.00    0.50    1.00                                      Sodium monofluorophosphate                                                                        0.85    0.85    0.85                                      Sodium saccharin    0.20    0.20    0.20                                      Formalin BP         0.04    0.04    0.04                                      Flavour oil         1.20    1.20    1.20                                      Water               9.91    9.90    11.91                                     d.sub.o spacing (nm)                                                                              3.4     3.8     3.6                                       % wt liquid crystal phase                                                                         0.3     3.1     2.1                                       ______________________________________                                    

EXAMPLE 15

This example shows that toothpastes having surfactant present in theform of a liquid crystal phase with low d_(o) spacing result in asuperior retention of an antimicrobial agent on the teeth than dotoothpastes for which the d_(o) value is higher.

In this in vitro procedure human molar teeth were used. The area oftooth exposed to the test toothpaste was standardised as follows. Eachtooth was cut in half vertically and each half was covered in wax,applied with a camel hair brush, with the exception of a 6 mm² windowleft uncovered on the enamel surface of each half tooth.

Toothpastes were delivered as 50% (w/v) slurries prepared freshly on theday of the test as follows. The diluent used was a mixture of ethanoland water (1:2 v/v) with ³ H-Triclosan dissolved to give a final levelof Triclosan in the toothpaste/diluent slurry of 20% greater than thetotal content of the paste being tested. For example, 5 g of aformulation containing 2 mg Triclosan/g paste (i.e. 10 mg Triclosan) wasslurried with 5 ml of the ethanol/water mix containing an additional 2mg ³ H-Triclosan.

The volume of the test slurry used in each case was 30 μl; this wassufficient to cover the tooth window and was applied for 1 minute. Afterthis application the tooth was washed for 45 seconds in water (2 ml).The wax was then removed and discarded, and the tooth washed further,twice in ethanol (2 ml) for 45 seconds and once in acidified ethanol (2ml:conc HCl/ethanol 1/9 v/v) for 30 minutes. The radioactivity collectedin the final two ethanol rinses and in the acid ethanol wash wasmeasured in a Packard Tricarb 4530 Scintillation Counter withappropriate quench correction, using Insta-gel Liquid ScintillationCocktail (United Technologies Packard). This was then expressed as thequantity of Triclosan binding to the tooth surface in the exposedwindow.

Appropriate control experiments demonstrated that radioactivity did notpenetrate the wax covering of the tooth surface. The binding ofTriclosan to the wax was ignored: the wax served simply as a shield andmeasurement of uptake was by the set area of tooth exposed by the waxwindow.

The results are summarised in Table VIII which represent the mean ofnine determinations for each toothpaste.

                  TABLE VIII                                                      ______________________________________                                                                      Triclosan                                                Triclosan     d.sub.o                                                                              uptake (μg/6 mm.sup.2                        Toothpaste                                                                             Content (%)   (nm)   tooth surface)                                  ______________________________________                                        Example 2A                                                                             0.2           4.0    1.36 ± 0.16*                                 Example 2A'                                                                            0.2           7.4    0.87 ± 0.04*                                 Example 1                                                                              0.5           4.0    1.28 ± 0.13**                                Example 1                                                                              0.5           6.3    0.89 ± 0.11**                                ______________________________________                                         *values significantly different at the 5% level                               **values significantly different at the 5% level                         

The batches of toothpastes 2A and 2A' used in this experiment weredifferent from those for which data are given in Table III.

EXAMPLE 16

This example concerns the firding that the amount of zinc retained inthe mouth after use of a toothpaste containing zinc citrate is greaterfor those toothpastes of which the lamellar spacing of the liquidcrystal surfactant phase is the smaller.

Nineteen panellists rinsed an aqueous slurry of toothpaste (1 gtoothpaste, 4 ml water) around the mouth for one minute. After this wasexpectorated and collected, a one minute 10 ml water rinse was carriedout and collected. By analysis it was determined what proportion of thezinc in the toothpaste was retained in the mouth after the rinsing.

The two toothpastes employed had the formulation given in Example 1.

The results are given in Table IX.

                  TABLE IX                                                        ______________________________________                                                    % Zinc Retained                                                   d.sub.o (nm)                                                                              in the mouth                                                      ______________________________________                                        4.0         26%*                                                              6.3          6%*                                                              ______________________________________                                         *values significantly different at the 5% level                          

Demonstration of long term plaque reduction and gum health benefit

The toothpaste used in this study was that of Table 1 having a d_(o)spacing of 4.3 nm.

The effect of the extended use of a dentifrice containing 1 % zinccitrate and 0.5 % Triclosan on plaque accumulation and gingival healthwas investigated.

The study was divided into two parts, i.e. a four-week prestudy periodto reduce the influence of motivation and professional cleaning wasfollowed by a ten-week experimental period. During the prestudy period,the participants used a placebo dentifrice which had the samecomposition as the test toothpaste except that the zinc citrate andTriclosan were omitted. The ten-week experimental period was dividedinto two four-week periods, separated by a two-week interval. During thetwo four-week experimental periods the participants used the test andplacebo dentifices in a double blind crossover design experiment. Thetwo-week interval was adopted in order to minimise the influence ofcarryover effects.

Volunteers were screened prior to participation in the study. Thescreening procedure was as follows. The partial recording schemerecommended by Cowell et al in J Clinical Periodontology, 1975, 2,231-240 was used to select panellists in which the six specific teethconcerned were free of overt caries and had associated pocket depths ofless than 3.5 mm when probed using the WHO probe(WHO stands for WorldHealth Organisation). In addition, selected subjects had to exhibit atleast a minimal level of gingival inflammation (more than 7 bleedingpoints out of 24 sites) to allow the demonstration of any improvement.Twenty males and twenty-nine females aged between 23 and 55 yearsparticipated in the study. No oral hygiene instructions were given butthe participants were encouraged to use sufficient dentifrices to coverthe head of the toothbrush (approximately 1.5 g).

Plaque was assessed using the Plaque Index according to Silness and Loe(Acta Odont.Scandinavia, 1964. 22, 121-35). Gingival inflammation wasassessed by the Gingival Index described by Loe (J. Periodontology, 196738, 610-16) and a modification of the Bleeding Index suggested by Cowellet al (J.Clinical Periodontology, 1975, 2, 231-240). Pocket depths wererecorded using 0.5 mm graduated plasticstrips 1.0 mm in width (Smith,British Dental J., 1975, 139, 369). Assessments were performed on thebuccal, mesial, distal and lingual surfaces of representative teeth (2molars, 2 premolars and 2 incisors) as suggested by Ramfjord (J.Periodontology, 1959, 30, 51-59).

First, the teeth were professionally cleaned to remove all traces ofsupra and subgingival plaque and calculus. The participants were thenprovided with placebo dentifrice and new brushes. The teeth were alsoprofessionally cleaned at the second examination which formed thebaselines for the first experimental period of the crossover. TheBleeding and Plaque data recorded at this examination were used toallocate the panellist to one of the groups so that the two balancedgroups were formed (Table X). One group was provided with the testdentifrice and the other group with the placebo, each to be used forfour weeks. Following this period, the clinical parameters werereassessed and the placebo dentifrice was used for two weeks to avoidany carryover effects arising from the test dentifrice prior to thesecond phase of the crossover. Clinical examination and professionalcleaning preceeded the second experimental phase. Each participant wasthen given their second dentifrice. Participants were again examined atthe end of this period.

The means of the plaque, gingival and bleeding indices for the four-weekprestudy period are given below in Table X.

                  TABLE X                                                         ______________________________________                                        Plaque Index   Gingival Index                                                                              Bleeding Index                                   ______________________________________                                        Baseline                                                                              0.87       1.00          0.47                                         Four-week                                                                             0.77       0.99          0.49                                         ______________________________________                                    

The means of the plaque, gingival and bleeding indices for eachfour-week experimental period and for the overall study (n=41) for bothdentifrices are given below in Table XI.

                  TABLE XI                                                        ______________________________________                                                 End of First                                                                           End of Second                                                        Experimental                                                                           Experimental                                                                              Mean of                                                  Period   Period      Total Group                                     ______________________________________                                        Plaque Index                                                                  Placebo    0.91       0.91        0.91                                        Test Dentifrice                                                                          0.67       0.67        0.67                                        Stat. signif.P>                                                                          0.05       0.05         0.001                                      Gingival Index                                                                Placebo    0.92       0.93        0.92                                        Test Dentifrice                                                                          0.75       0.71        0.73                                        Stat. signif.P>                                                                          0.06       0.01         0.001                                      Bleeding Index                                                                Placebo    0.49       0.54        0.51                                        Test Dentifrice                                                                          0.39       0.42        0.41                                        Stat. signif.P>                                                                          0.09       0.01         0.001                                      ______________________________________                                    

The results shown in Table XI demonstrate a significant reduction inplaque accumulation and improvement in gingival health for the testdentifrice copared to the placebo.

Demonstration of enhanced inhibition of plaque metabolism

This study demostrates that a toothpaste composition according to theinvention having a liquid crystal surfactant phase of low lamellarspaceing provides an enhanced inhibition of plaque metabolism comparedwith one having a liquid crystal surfactant phase of high lamellarspacing. Inhibition of plaque metabolism can be assessed by measuringthe pH fall of plaque after a glucose rinse. The toothpastes used inthis cross-over study were those of Table I having a d_(o) spacing of4.0 and 6.3 nm respectively, and were tested on ten panellists whorefrained from toothbrushing for 24 hours prior to the experiment toallow plaque to accumulate. Each participant rinsed for 1 minute with 13g of a 25% solution of the appropriate toothpaste in water. After 1 houra plaque sample was collected, comprising of aliquots of plaque removedfrom at least eight incisor teeth. The pH of this sample dispersed in 5μl deionised water was determined using an M1-410 Microcombination pHProbe (Microelectrodes Inc USA), the value being recorded 30 secondsafter introduction of the pH electrode. The remaining plaque on theteeth was subjected to a 1 minute rinse with a 15% glucose solution. Asecond plaque sample was taken 5 minutes later and the pH measured asbefore. After an interval of 12 days the procedure was repeated with thepanellists using the other test product.

The mean values for the pH drop caused by the glucose challenge afteruse of the test toothpastes are shown in Table XII. The smaller pH dropassociated with the use of the product with the smaller d_(o) valueindicates that this toothpaste has a greater effect upon inhibition ofplaque metabolism.

                  TABLE XII                                                       ______________________________________                                        d.sub.o spacing of liquid                                                                    Mean drop in plaque                                            crystal surfactant                                                                           pH after glucose                                               phase of toothpaste                                                                          challenge                                                      ______________________________________                                        4.0 nm         0.57*                                                          6.3 nm         0.84*                                                          ______________________________________                                         *values significantly different at the 5% level.                         

What is claimed is:
 1. A dentifrice composition, selected from the groupconsisting of a toothpaste, dental cream, or dental gel, effective toinhibit the growth of dental plaque comprisinga surfactuant; aparticulate abrasive agent in an amount of between about 5 and 60% byweight of the dentifrice composition; water in an amount between about25 and 60% by weight of the dentifrice excluding insoluble solids; andan anti-plaque agent consisting of an effective amount of asubstantially water-insoluble non-cationic antimicrobial agent ormixture thereof with a zinc salt having a water solubility greater than2×10⁻⁴ per 100 g of water at 25° C. and pH 7,characterized in that thereis present in the dentifrice composition a lamellar liquid crystalsurfactant phase having a lamellar spacing of less than 6.0 nm in anamount of at least about 0.2% by weight of the dentifrice composition,the lamellar spacing and percentage weight of the lamellar liquidcrystal surfactant phase being measured after a centrifugationseparation procedure, said separation procedure comprising: (1)sufficient centrifugation to separate the dentifrice composition intoits main phases including a liquid portion; followed by (2) sufficientultracentrifugation of the liquid portion so that the liquid portionseparates into layers and there is no substantial change in the volumesof the separated layers of the liquid portion, the lamellar liquidcrystal surfactant phase being present as one of the separated layers ofthe liquid portion.
 2. A dentifrice composition as claimed in claim 1,wherein the lamellar spacing of the liquid crystal surfactant phase isless than 5.0 nm.
 3. A dentifrice composition as claimed in claim 2,wherein the said lamellar spacing is less than 4.4 nm.
 4. A dentifricecomposition as claimed in claim 1, wherein said lamellar liquid crystalsurfactant phase is present in an amount of at least 0.3% by weight ofthe dentifrice composition.
 5. A dentifrice composition as claimed inclaim 4, wherein said lamellar liquid crystal surfactant phase ispresent in an amount of at least 0.5% by weight of the dentifricecomposition.
 6. A dentifrice composition as claimed in claim 1, whereinthe surfactant is an anionic surfactant.
 7. A dentifrice composition asclaimed in claim 6, wherein the surfactant is selected from the groupconsisting of sodium lauryl sulphate, sodium dodecylbenzene sulphonate,sodium lauroyl sarcosinate and mixtures thereof.
 8. A dentifricecomposition as claimed in claim 1, wherein the particulate abrasiveagent is selected from alumina and silica abrasives having a particlesize in the range of 2 to 20 microns.
 9. A dentifrice composition asclaimed in claim 1, wherein in the formulation of the dentifrice thereis also included as an ingredient from 0.1 to 3% by weight of sodiumchloride or a water-soluble electrolyte salt, other than afluorine-containing salt, in an equivalent molar cation concentrationeffective to reduce the lamellar spacing of the liquid crystalsurfactant phase to below 6.0 nm, but in an amount insufficient toresult in the destruction of the liqid crystal surfactant phase.
 10. Adentifrice composition as claimed in claim 9, wherein in the fromulationof the toothpaste there is included 0.1 to 1% by weight of sodiumchloride.
 11. A dentifrice composition as claimed in claim 1, whereinthe antimicrobial agent is selected from the group consisting ofphenolic compounds, bisphenolic compounds, halogenated diphenyl ethers,benzoate esters and carbanilides.
 12. A dentifrice composition asclaimed in claim 1, wherein the antimicrobial agent has a solubility inwater at 25° C. of less than 0.5%.
 13. A dentifrice composition asclaimed in claim 12, wherein the antimicrobial agent has a solubility inwater at 25° C. of less than 0.1%.
 14. A dentifrice composition asclaimed in claim 11, wherein the antimicrobial agent is Triclosan.
 15. Adentifrice composition as claimed in claim 1, wherein the antimicrobialagent is present in an amount of 0.01 to 5% by weight.
 16. A dentifricecomposition as claimed in claim 1, wherein the zinc salt has a watersolubility greater than 1×10⁻² g per 100 g of water at 25° C. and pH 7.17. A dentifrice composition as claimed in claim 1, wherein the zincsalt is a salt of an orgainic acid selected from mono-, di-, andtri-carboxylic acids, alphahydroxy carboxylic acids and amino acids. 18.A dentifrice composition as claimed in claim 17, wherein the zinc saltis zinc citrate.
 19. A dentifrice composition as claimed in claim 1,wherein the zinc salt is present in such amount as to provide from 0.05to 1.5% of zinc by weight of the composition.
 20. A dentifricecomposition as claimed in claim 1, comprising 0.05 to 3% Triclosan, 0.3%to 1.5% zinc citrate, 0.2 to 1% sodium chloride and 1 to 3% sodiumlauryl sulphate.
 21. A dentifrice composition as claimed in claim 1,comprising agout 1% to about 3% by weight of an anionic surfactantselected from the group consisting of sodium lauryl sulphate, sodiumdodecylbenzene sulphonate, sodium lauroyl sarcosinate and mixturesthereof, an anti-plaque agent consisting of from about 0.01% to about 5%by weight Triclosan or a mixture of said Triclosan with about 0.2% toabout 2% by weight zinc citrate, about 0.1% to about 3% by weight sodiumchloride, about 5% to about 60% by weight of an abrasive selected fromalumina and silica abrasives, about 15% to 70% by weight of sorbitolsyrup and about 0.1% to 5% by weight of flavour oil.
 22. A dentifricecomposition as claimed in claim 1, wherein the lamellar spacing ismeasured within a month of manufacturing the dentifrice composition.